IncobotulinumtoxinA Demonstrates Safety and Prolonged Duration of Effect in a Dose-Ranging Study for Glabellar Lines

October 2020 | Volume 19 | Issue 10 | Original Article | 985 | Copyright © October 2020


Published online September 30, 2020

Martina Kerscher PhDa, Sabrina Fabi MDb, Tanja Fischer MDPhD, Michael Gold MDd, John Joseph MDe, Welf Prager MDf, Berthold Rzany MD ScMg, Steve Yoelin MDh, Susanna Roll Dr. med, Gudrun Klein PhDi, Corey Maas MD PhDj

aUniversität Hamburg, Hamburg, Germany bCosmetic Laser Dermatology, San Diego, CA cHaut- & Lasercentrum, Potsdam, Germany dGold Skin Care Center, Tennessee Clinical Research Center, Nashville, TN eJohn Joseph MD, Private Practice, Beverly Hills, CA fPrager and Partner Dermatologische Praxis, Hamburg, Germany gHautärzte RZANY&HUND, Berlin, Germany hMedical Associates, Inc., Newport Beach, CA iMerz Pharmaceuticals GmbH, Frankfurt am Main, Germany jThe Maas Clinic, San Francisco, CA

Abstract
Background: Recently reported clinical data provides evidence that increasing the dose of botulinum toxin A increases the duration of efficacy. A 2-stage Phase 2, randomized, double-blind study investigated the duration of effect and safety of IncobotulinumtoxinA (INCO; Xeomin®, Bocouture®; Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany) at doses higher than the approved 20 units (U) for glabellar frown lines (GFL). Primary safety and efficacy endpoints of Stage 1 are reported here.

Methods
: 151 subjects with moderate-to-severe GFL were randomized 1:2:2 to receive a single treatment with 20U, 50U, or 75U INCO. The primary efficacy endpoint was median duration of at least 1-point improvement from baseline as assessed by investigator at maximum frown on the Facial Wrinkle Scale.

Results
: The median duration of effect was 185 days for the 50U dose group (95% CI:[182, 205]) and 210 days for the 75U dose group (95% CI:[182, 217]). Duration of effect was significantly longer for 75U vs 50U (P=0.0400) and 20U (P=0.0166) despite the study not being powered for confirmatory statistical significance testing between the dose groups. Duration of effect was also longer for 50U vs 20U, however; statistical significance was not reached (P=0.4349). The incidence of treatment-related adverse events was low across all doses (20U:2[6.7%], 50U:6[10.0%] and 75U:8[13.1%]).

Conclusions
: These results demonstrate a dose effect of at least 6 months duration with higher doses in the majority of GFL subjects. All doses were well tolerated and safety was consistent with the known safety profile of 20U INCO for GFL.

J Drugs Dermatol. 2020;19(10):985-991. doi:10.36849/JDD.2020.5454

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INTRODUCTION

IncobotulinumtoxinA (INCO; Xeomin®, Bocouture®; Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany) is the only commercially available botulinum toxin A (BoNT/A) preparation free from complexing proteins.1 INCO is currently approved in worldwide markets and in the United States to treat glabellar frown lines (GFL) at a dose of 20 Units (U) and in the European Union at a dose of 20–30U.

The duration of effect for glabellar lines is approximately 3–4 months in Phase 3 studies investigating the FDA-labeled dose of 20U for INCO, OnabotulinumtoxinA (ONA; Botox®/Vistabel®, Allergan Inc.) and PrabotulinumtoxinA (PRA; Nabota®, Daewong Therapeutics, Korea/ Jeuveau®, Evolus Inc., USA/Nuceiva®, Evolus Inc., Canada, Europe), as well as the FDA-labeled dose of 50U for AbobotulinumtoxinA (ABO; Dysport®/Azzalure®, Ipsen Pharma, Wrexham, UK).2-4 In the first large, randomized, multicenter, double-blind study to investigate FDA-labeled doses, equivalence between INCO and ONA in the treatment of GFL at the 20U dose in 250 subjects was demonstrated using an investigator-assessed responder rate (≥1-point improvement from baseline on the Facial Wrinkle Scale [FWS] at maximum frown). Similar efficacy profiles were demonstrated at all timepoints (1, 2, 3, and 4 months). Additionally, patient satisfaction was high (>90%) for both treatment groups. In both studies, INCO and ONA were found to be well tolerated.5 This study supported an earlier head-to-head study demonstrating non-inferiority to ONA in 381 subjects.6